Preclinical Data Shows Anti-Siglec-15 Treatment Improves Bone Quality in Osteogenesis Imperfecta Mice

BELTSVILLE, Md., Nov. 19, 2024 – NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company dedicated to developing innovative cancer therapies, recently presented preclinical data on NC605, a novel anti-Siglec-15 (S15) antibody, at the Osteogenesis Imperfecta Federation Europe virtual Investigator Meeting on November 15, 2024. The data showcased NC605's effectiveness in enhancing the quality of bone with superior mechanical properties, specifically for Osteogenesis Imperfecta (OI), commonly known as brittle bone disease.

Osteogenesis Imperfecta (OI) is a rare genetic disorder characterized by high bone turnover, abnormal bone formation, fragility, and frequent fractures. Currently, there is no cure for OI. Existing treatments mainly focus on anti-resorptive strategies that inhibit both bone loss and formation, leading to increased bone density but compromised bone quality. In contrast, NC605 aims to inhibit bone loss while enhancing osteoblast recruitment, resulting in new bone generation with superior quality and density.

The preclinical study assessed fracture incidence and bone quality in male and female OI mice (oim) treated with 20 mg/kg of NP159, a surrogate antibody for NC605. The results were compared with control groups. Key findings from the study include:
- In treated mice, 90% of male oim and 80% of female oim showed no fractures post-sacrifice, compared to 85% of males and 55% of females in the control groups.
- Both male and female treated oim populations exhibited increased trabecular and cortical tissue mineral density and cortical bone mineral density, collectively enhancing bone quality and mechanical properties.
- Specifically in treated male oim populations, there was an increase in trabecular bone volume fraction, an increase in the number of trabeculae, decreased separation between trabeculae, and increased cortical thickness. These changes resulted in increased maximum load and stiffness, indicating stronger mechanical bone strength.

Solomon Langermann, Ph.D., Chief Scientific Officer at NextCure, commented on the findings: "We have once again demonstrated that NP159, a surrogate murine antibody for NC605, reduces fracture incidence in both male and female OI mice. Observing the sexual dimorphism in OI, we noted improved bone quality particularly in treated male mice." He further emphasized the potential of NC605 as a transformative treatment for both female and male OI patients.

The preclinical data were generated in collaboration with Dr. Cathleen Raggio from the Hospital for Special Surgery in New York. The promising results suggest that NC605 could significantly improve the management of OI by enhancing bone quality and mechanical properties, thereby reducing the risk of fractures.

NextCure, Inc. focuses on developing therapies that employ unique mechanisms of action, including antibody-drug conjugates, antibodies, and proteins, to treat cancer patients unresponsive to existing treatments. The company leverages its expertise in understanding biological pathways, biomarkers, and cell interactions within the tumor microenvironment to develop innovative therapeutic solutions.

This announcement underscores NextCure's commitment to advancing medical research and developing effective treatments for complex diseases like OI. As the company progresses with NC605, it holds the potential to offer new hope to patients with brittle bone disease, aiming to improve their quality of life by reducing fracture risks and enhancing bone strength.